Increasing cross-linkages of proteins have been proposed as one of the more plausible causes of aging. Suddenly, this began to make good sense, for we have identified testis-organizing H-Y plasma membrane antigen of man as extremely hydrophobic polymers of M.W. 18,000 subunit formed exclusively by interchain disulfide bridges, and that the largest class of polymers loses the receptor binding activity, therefore, testis-organizing function. Furthermore, the very fact that beta2 microglobulin (-), HLA antigen (-) Daudi human male Burkitt lymphoma cells excrete H-Y antigen and several other hydrophobic proteins into the culture medium, instead of maintaining them on the plasma membrane, supports my 1977 proposal that H-Y and other organogenesis-directing proteins are in physical association with beta2m-MHC antigen dimers on the plasma membrane. We intend to study on cultured mouse testicular Sertoli cells that normally excrete H-Y antigen (Ref. 2), whether aging causes excessive polymerization of M.W. 18,000 H-Y antigen subunit that renders them defunct in their testis-organizing function. We also intend to study whether such excessive polymerization, occuring on the thymic epithelial plasma membrane, disturbs the instruction to the cell-mediated immune system with regard to the self versus nonself MHC-restricted discrimination.